The cells which we propose to study are part of a diffuse endocrine system which has the general characteristics of being capable of amine precursor uptake and decarboxylation (APUD) and producing polypeptide hormones. Although the physiological role of APUD cells in most of the organs in which they occur is well documented, the function and secretory products of the APUD cells of the lung are not known. The difficulty in studying the APUD cells of the lung is that they are sparsely distributed throughout the lung. We propose to quantitate systemically the anatomic distribution of the APUD cells of the lung. We will begin with a fluorescent microscopic survey of the formaldehyde-induced fluorescence (FIF) that amine primed APUD cells emit. FIF is a quick and efficient way to surve a large amount of tissue in order to obtain an adequate sampling of these cells. We will verify the presence of the APUD cells with the electron microscope. As these quantitative studies are in progress we will investigate two different procedures which should make it possible to go directly with the same tissue, from the fluorescent microscope to the electron microscope for verification that the FIF cell is indeed an APUD cell. With the classical Falck-Hillarp procedure, it is not possible to do this because the preservation of the freeze-dried material is not suitable for electron microscopy. Once we have quantitated the location of the APUD cells, we will attempt to increase the number of APUD cells by stimulating hyperplasia with such known mucosal irritants as nitrogen dioxide and diethynitrosamine (DEN). These APUD cell hyperplasias as well as normal trachea will be studied in organ culture in the presence and absence of nerve growth factor (NGF) and DEN. The increased number of APUD cells will make it easier to study the anatomic proximity of APUD cells to secretory cells and may indicate factors which control their numbers.